Addressing the Common Pitfalls of D-Dimer Testing in Pulmonary Embolism Diagnosis

Firmin Camargo^*
*Correspondence: Firmin Camargo, Department of Internal Medicine, Cairo University, Cairo 12613, Egypt, Email:

Introduction

Pulmonary Embolism (PE) remains a significant cause of morbidity and mortality worldwide, necessitating timely and accurate diagnosis. The diagnosis of PE can be challenging, particularly in patients with nonspecific symptoms that overlap with a variety of other diseases. D-dimer testing has emerged as a pivotal tool in the diagnostic workup of suspected pulmonary embolism due to its ability to rule out the condition in certain patient populations. However, while the D-dimer test provides significant advantages, it also has limitations and common pitfalls that must be understood and mitigated to avoid misdiagnosis. This aims to explore the use of D-dimer testing in pulmonary embolism diagnosis, focusing on the common pitfalls associated with the test. By addressing these issues, healthcare providers can better utilize this tool to improve diagnostic accuracy, optimize patient care and reduce the risk of complications related to delayed or incorrect diagnosis [1].

Description

D-dimer is a fibrin degradation product produced when a blood clot breaks down. It is a useful biomarker that can indicate the presence of active clot formation and breakdown. In the context of PE, D-dimer testing has been established as an essential part of the diagnostic algorithm, especially in patients with low or intermediate clinical probability. D-dimer tests have a high sensitivity, meaning that a normal (or negative) result significantly reduces the likelihood of PE. This is particularly useful in ruling out PE in patients with a low pre-test probability, avoiding unnecessary imaging studies and treatments. The test is often combined with clinical assessment tools such as the Wells Score or Geneva Score to stratify the patient’s risk. If the clinical score suggests a low risk of PE, a negative D-dimer result can reliably exclude the diagnosis. Despite its usefulness, the D-dimer test is not fool proof. While it is a valuable diagnostic aid, its interpretation can be influenced by various factors, which may lead to false positives or false negatives. A significant factor influencing the interpretation of D-dimer results is the age of the patient. As individuals age, their D-dimer levels naturally increase, even in the absence of any pathological clotting events. This age-related increase in D-dimer levels can lead to false positives, especially in elderly patients. In these cases, clinicians may be more inclined to perform unnecessary imaging or therapeutic interventions, potentially exposing patients to avoidable risks [2]. D-dimer levels are not specific to pulmonary embolism and a wide range of conditions can elevate D-dimer levels. Bacterial and viral infections, including pneumonia, can cause elevated D-dimer levels due to systemic inflammation and clot formation as part of the body’s response to infection. Recent trauma, surgical procedures, or even minor injuries can trigger fibrinogen breakdown, resulting in raised D-dimer levels. Pregnant women, particularly in the later stages of pregnancy, may show elevated D-dimer levels as a normal physiological change. Malignancy is a well-known cause of elevated D-dimer levels, particularly in cancers associated with hypercoagulability, such as lung, pancreatic and ovarian cancers. Chronic kidney disease and other renal impairments can lead to increased D-dimer production, further complicating the diagnostic process. Thus, elevated D-dimer levels must be interpreted in conjunction with a thorough clinical assessment. Relying solely on a positive D-dimer result without considering other potential causes can lead to false positives, unnecessary imaging and misdiagnosis. While the D-dimer test has high sensitivity, it suffers from poor specificity, especially in high-risk patients. For instance, patients with known cancer, severe infections, or recent surgeries may have elevated D-dimer levels even in the absence of pulmonary embolism. In these cases, a positive D-dimer result may lead to the overuse of imaging studies such as CT Pulmonary Angiography (CTPA) or ventilationperfusion (V/Q) scans, which expose patients to unnecessary risks such as radiation exposure, contrast nephropathy and anxiety [3]. Another pitfall in D-dimer testing is the variability in assay methods. Different laboratories may use different D-dimer assays and each test may have varying sensitivity, specificity and cut-off values. This lack of standardization can lead to inconsistencies in results and difficulty in interpreting the test across different clinical settings. To mitigate this issue, it is essential for healthcare providers to be familiar with the specific D-dimer test used in their institution and understand its characteristics. Standardization of testing methods and the establishment of clear protocols for interpreting D-dimer results can help reduce the potential for diagnostic errors. One of the most significant pitfalls in the use of D-dimer testing is over-reliance on the test as a standalone diagnostic tool. While D-dimer testing is an important component of the diagnostic workup for pulmonary embolism, it should not be used in isolation. The test must be interpreted in the context of the patient’s clinical history, risk factors and other diagnostic modalities. For instance, if a patient presents with classic symptoms of PE, such as chest pain, dyspnea and haemoptysis, but has a negative D-dimer result, the clinician should not rule out PE solely based on the test. Imaging studies such as CTPA or V/Q scans may be necessary to confirm or exclude the diagnosis [4,5].

Conclusion

D-dimer testing is a valuable tool in the diagnosis of pulmonary embolism, particularly for ruling out the condition in patients with low pre-test probability. However, like any diagnostic tool, it has limitations and is prone to common pitfalls that can lead to false positives, false negatives and unnecessary testing. By understanding these pitfalls and integrating D-dimer testing into a comprehensive diagnostic approach, clinicians can make more accurate diagnoses, minimize the risk of misdiagnosis and provide more appropriate care for patients suspected of having pulmonary embolism. A thoughtful, evidence-based approach to the use of D-dimer testing, in conjunction with clinical assessment and imaging modalities, is essential to improving patient outcomes and avoiding unnecessary interventions. Through continuous education and adherence to best practices, healthcare providers can enhance the reliability of D-dimer testing and ensure its optimal use in clinical practice.

Acknowledgement

None

Conflict of Interest

None

References

1. Freund, Yonathan, Fleur Cohen-Aubart and Ben Bloom. "Acute pulmonary embolism: a review." Jama 328 (2022): 1336-1345.

Google Scholar, Crossref, Indexed at

2. Lippi, Giuseppe, Gianfranco Cervellin, Ivo Casagranda and Benedetto Morelli, et al. "D-dimer testing for suspected venous thromboembolism in the emergency department. Consensus document of AcEMC, CISMEL, SIBioC and SIMeL." Clin Chem Lab Med 52 (2014): 621-628.

Google Scholar , Crossref, Indexed at